The Non-Linear Factor: People – Process Risk Assessments (Part 5)

Editor’s Note: This is part 5 of a 7 part series on Process Risk Assessments.

Last week, we saw how capturing uncertainty and detectability risk brings clarity and dimension while assessing risk when used appropriately. These elements are especially important when creating a data-driven risk assessment approach, like those enabled in QbDVision.

This week, we will look at the practical aspects of process risk assessments from a different lens: that of the people executing or using these tools.

Let’s review!

Introduction

A common question that arises when designing a risk management plan relates to the appropriate number of risk levels. Should there be 3 or 5 or 10 levels? Should we use a square matrix (5×5) or non-square (5×10)? It is common practice to select 4 or 5 levels. Fewer than 4 levels may not provide sufficient resolution and more than 5 leads to difficulties deciding between the minute difference in risk. That being said, the FDA uses a 3×3 matrix for its internal CAPA system.

While there is no prescriptive guidance available to answer this question, it is important to first acknowledge an important aspect of answering this question is people. Risk Assessments are a data-based, but still subjective, evaluations of a situation by subject matter experts (SMEs). And, almost always, the process for defining risk is collaborative in nature. People get together and discuss, debate, and decide on risks. These evaluations need to be understood, managed, and updated by the SMEs and external stakeholders, especially when being used to define the scope of work. The results need to be understood in the broader context of the organization that will act upon them in the subsequent parts of the development process. While it is best for the principles and rules of assignment to be algorithmic and data-driven using a meritocratic process for deciding on the ultimate values, the final results need to be simple and clear to guide future actions.

Ultimately, a risk assessment results in a categorization. Fundamentally, it is a method for information chunking, distilling, and grouping complex sets of information for communication and decision-making purposes. Therefore, an important consideration for selecting the dimensions of risk is its intended use. Will people understand it?

Do you have a shared organizational lexicon to accurately describe nuances in risk across a 10×10 matrix? And, most importantly, will your people know how to manage the variances between them? Do you have time, resources, and capital to manage the complexity of such a large grouping? The answer to these questions will undoubtedly vary from team-to-team and organization-to-organization. And they may evolve over time as your organization grows and learns. Simplicity is a good long term bet. QbDVision provides flexibility to define whatever structures suit your organization. Each element of your schema can be annotated with risk and score labels, as well as clear descriptions that are provided inline to users when selecting risk values.

Justifications

Concordant with evaluating your team’s ability to understand the risk rating broadly is the assessment of their ability to know why it was given that assignment in the first place. Traditional matrix-based assessments are often lacking in their ability to record justifications. That is often because the same tool for viewing risk is being used for assessing risk: it’s just one spreadsheet. As seen in the Risk Assessment Examples for Manufacturing Processes in from earlier in our series, there is significant depth to the justification for each level. Imagine making that assessment, but then only having “High” as the result. That is an important aspect that is lost in today’s Excel-based processes. One way teams try to overcome this is by overloading this information in the risk schema itself – i.e., making a 10×10 to attempt to capture more detail about the variances. QbDVision makes it easy to capture layered and historical justifications at each level, similar to what you see in the table below. This way, when re-evaluating risk, you can drill into those justifications and decide: did we add a new source of risk, has the risk of a known source changed, etc. When you separate the justification behind this risk from the risk rating, it is easier to simplify your risk schema.

Risk Assessment Examples for Manufacturing Processes

Risk ElementNon-Pharma ExamplePharma ExampleManufacturing Example
HazardGas leakExcessive degradation of drug productCO2 stripping time is out-of-specification (OOS)
Potential CausesCorrosion; incorrect installation of valveExtended excursion from recommended storage temperatures.CO2 sparging not working correctly
Exposure (P1) or Probability of Hazardous Situation occurringProbability of gas leak in roomProbability of excessive degradationProbability of CO2 stripping time being OOS
Hazardous SituationPeople or equipment in room with gas leakDrug product has excessive degradation when the patient takes it, leading to an adverse reaction.CO2 stripping time is OOS during the manufacturing process.
HarmExplosion that injures people or damages equipmentAdministration of drug product with excessive degradation leads to adverse eventCO2 stripping time OOS causes dissolved CO2 OOS in production bioreactor
Probability or Likelihood of Harm (P2)Probability of explosion occurring when there is a gas leakProbability of adverse event when patient takes drug that has excessive degradationProbability of dissolved CO2 being OOS if CO2 stripping time is OOS
Severity of Harm (S)Explosion leads to death or irreparable damage of equipmentDegradation products in drug product lead to severe allergic reactionHow sensitive is dissolved CO2 to CO2 stripping time
Probability of Occurrence of Harm (P1 x P2)Probability of a gas leak and a subsequent explosionProbability of drug having excessive degradation and adverse event occurringProbability of CO2 stripping time OOS and dissolved CO2 OOS
Risk (S x P1 x P2)Risk to personnel if there is a gas leak that leads to an explosionRisk to the patient if they take a drug with excessive degradation and an adverse event occurs.Degree of dissolved CO2 OOS if CO2 stripping time is OOS
Mitigation StrategiesPersonnel properly trained on installation; use of stainless steel components to minimize corrosionAddition of excipients to inhibit degradationConfirm correct sparger design/type for scale
Control StrategiesSensor installed in the laboratory with an alarm to detect the presence of gas in the airUsing temperature control devices during shipping to track temperature excursionUse CO2 sensor to monitor dissolved CO2 in-process

Structure

Another consideration for deciding on the dimensions of your risk schema is organizational comparability. We often see different departments or groups with different risk schemas. While there can be sound reasoning for the variances, it is important to weigh the benefits of normalization efforts. With the prevalence of paper or document-based approaches, it is not surprising to see teams take this type of disjointed approach. Why spend the effort to normalize when there is little chance of doing a cross-project or drug comparison? As the industry continues to move towards structured platforms, like QbDVision, this will become more important. You’ll want to take Risk Assessments coming from a Materials Management group and evaluate them in context to your process development. When it only takes a click of a button to evaluate risk across projects or phases or to compare to organizational history or knowledge, you’ll unlock the power of this normalizatio

A final question often encountered relates to the definitions of each discrete category and the individual layers. QbDVision provides three default RMP configurations, 3×3, 4×4, and 5×5 with accompanying definitions. Each default RMP can be copied and edited to create a new RMP configured to your organization’s needs.

Conclusion

In the end, people and their individual thoughts are a critical, non-linear (and uncontrollable!) element of assessing risk. Prior knowledge, experience, intuition, pattern matching skills, and recall abilities remain essential to assessing and acting on risk information. Applying those skills to a structured and data-driven approach can accelerate and maximize risk understanding. When designing that structure, it’s important to advocate for a strong foundation and a simple and concise result.

Next week, we will discuss how QbDVision risk management plans can be configured to handle the topics and situations reviewed in this series.

This post is part 5 of 7 in a series on practical risk management for pharmaceutical process development.

Mark Fish

Managing Director, Scientific Informatics, Accenture

Mark Fish is Managing Director and Global Lead for Accenture’s Scientific Informatics Services Business. Mark has over 25 years of experience in leadership roles in Accenture, Brooks Life Sciences and Thermo Fisher Scientific delivering innovative solutions to the pharmaceutical sector and is passionate about drug discovery and development, translation research and manufacturing transformation. Mark has extensive experience in agile software development, data strategy, process engineering and robotic automation for research, analytical development and quality control in Life Sciences.

Chris Puzzo

Solution Architect, Digital & Data, Zaether

Chris is a Solution Architect with Zaether, focusing on delivering next-generation digital and data solutions for GxP Life Sciences customers. Chris has previously held technical operations roles within multiple gene therapy manufacturers, including Thermo Fisher Scientific’s CDMO organization where he supported various capital projects including the design, build, and startup of new GxP manufacturing capacity.

Victor Goetz, Ph.D

Executive Director, TS/MS New Modalities and Data Strategy, Eli Lilly and Company

Victor Goetz, Ph.D. is the Executive Director of Technical Services New Modalities and Data Strategy at Eli Lilly and Company. He has over 35 years of industry experience in developing and commercializing nine novel medicines to enhance the exchange of knowledge needed to speed the delivery of new medicines to patients. Dr. Goetz holds a BS in chemical engineering from Stanford University and a PhD in chemical and biochemical engineering from the University of Pennsylvania.

Rachelle Howard

Director of Manufacturing Systems Automation and Digital Strategy, Vertex Pharmaceuticals

Rachelle is the Director of Manufacturing Systems Automation and Digital Strategy for Vertex’s Small Molecule Manufacturing Center. She oversees the site Automation Engineering function and has co-led Vertex’s global Digital Manufacturing Transformation program since 2019. She leads several initiatives related to data integrity, data management, and employee education. Rachelle is a graduate of Tufts University and the University of Connecticut where she has degrees in Chemical Engineering and a PhD in Process Control.

Vijay Raju

Vice President, CMC Management, Flagship Pioneering

Vijay currently leads CMC activities to deliver on Pioneering Medicines portfolio. The portfolio is built on Flagship Pioneering’s bio-platforms covering multiple modalities (small molecules, biologics, cell & gene therapies). Vijay was previously in technical leadership roles at Novartis.

Greg Troiano

Head of cGMP Strategic Supply & Operations, mRNA Center of Excellence, Sanofi

Greg serves as Head of cGMP Strategic Supply and Operations at the mRNA Center of Excellence at Sanofi, where he is responsible for all aspects of clinical production and raw material supply chain. He joined Sanofi via acquisition of Translate Bio, where he was Chief Manufacturing Officer and responsible for Technical Operations. Over his 20+ year career in the drug delivery field, Greg had various roles leading the pharmaceutical development of complex formulations, including numerous nano- and microparticle based systems. Greg received his MSE and BS in Biomedical Engineering from The Johns Hopkins University and was elected and inducted into the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in 2020 for recognition of his accomplishments in drug delivery.

Pat Sacco

Senior Vice President Manufacturing, Quality, and Operations, SalioGen

Pat is a Biotechnology technical operations executive with 30+ years of experience leading and managing technical operations functions at numerous innovative companies in the biotech and life sciences industries. He has a passion for advancing and implementing best practices in pharmaceutical manufacturing.

Diana Bowley

Associate Director, Data & Digital Strategy, AbbVie

Diana is the Associate Director, Data & Digital Strategy in S&T-Biologics Development and Launch leading the organization’s Digital Transformation since October 2021. She joined AbbVie in 2012 in the R&D-Discovery Biologics group focused on antibody and multi-specific protein screening and engineering, leading multiple programs to the cell line development stage. In 2017 she joined Information Research and led a team of IT professionals who supported AbbVie’s Discovery Scientists in Biotherapeutics, Chemistry, Immunology and Neuroscience. She has a PhD in Molecular Biology from The Scripps Research Institute and Bachelor of Science in Chemistry from The University of Northern Iowa.

Robert Dimitri, M.S., M.B.A.

Director Digital Quality Systems, Thermo Fisher Scientific

Robert Dimitri is a Director of Digital Quality Systems in Thermofisher’s Pharma Services Group. Previously he was a Digital Transformation and Innovation Lead in Takeda’s Business Excellence for the Biologics Operating Unit while leading Digital and Data Sciences groups in Manufacturing Sciences at Takeda’s Massachusetts Biologics Site.

Devendra Deshmukh

Global Head, Digital Science Business Operations, Thermo Fisher Scientific

Devendra Deshmukh currently leads Global Business Operations for Digital Science Solutions at Thermo Fisher Scientific. In this role he oversees operations broadly for the business across its product portfolio and leads the global professional services, technical support, and product education teams.

Grant Henderson

Sr. Dir. Manufacturing Science and Technology, VernalBio

Grant Henderson is the Senior Director of Manufacturing Science and Technology at Vernal Biosciences. He has years of expertise in pharmaceutical manufacturing process development/characterization, advanced design of experiments, and principles of operational excellence.

Ryan Nielsen

Life Sciences Global Sales Director, Rockwell Automation

Ryan Nielsen is the Life Sciences Global Sales Director at Rockwell Automation. He has over 17 years of industry experience and a passion for collaboration in solving complex problems and adding value to the life sciences space.

Shameek Ray

Head of Quality Manufacturing Informatics, Zifo

Shameek Ray is the Head of Quality Manufacturing Informatics and Zifo and has extensive experience in implementing laboratory informatics and automation for life sciences, forensics, consumer goods, chemicals, food and beverage, and crop science industries. With his background in services, consulting, and product management, he has helped numerous labs embark on their digital transformation journey.

Max Peterson​

Lab Data Automation Practice Manager, Zifo

Max Petersen is the Lab Data Automation Practice Manager at Zifo responsible for developing strategy for their Lab Data Automation Solution (LDAS) offerings. He has over 20 years of experience in informatics and simulation technologies in life sciences, chemicals, and materials applications.

Michael Stapleton

Board Director, QbDVision

Michael Stapleton is a life sciences leader with success spanning leadership roles in software, consumables, instruments, services, consulting, and pharmaceuticals. He is a constant innovator, optimist, influencer, and digital thought leader identifying the next strategic challenge in life sciences, executing and operationalizing on high impact strategic plans to drive growth.

Matthew Schulze

Head of Digital Pioneering Medicines & Regulatory Systems, Flagship Pioneering

Matt Schulze is a Senior Director in the Flagship Digital, IT, and Informatics team, where he leads and manages the digital evolution for Pioneering Medicines. His role is pivotal in ensuring that digital strategies align with the overall goals and objectives of the Flagship Pioneering initiative.

His robust background in digital life sciences includes expertise in applications, informatics, data management, and IT/OT management. He previously spearheaded Digital Biomanufacturing Applications at Resilience, a CDMO start-up backed by Arch, where he established a team responsible for implementing global manufacturing automation systems, Quality Assurance applications, laboratory systems, and data management applications.

Matt holds a B.S. in Biology and Biotechnology from Worcester Polytechnic Institute and an M.B.A. from the Boston University Questrom School of Business, where he focused on Strategy and Innovation.

Daniel R. Matlis

Founder and President, Axendia

Daniel R. Matlis is the Founder and President of Axendia, an analyst firm providing trusted advice to life science executives on business, technology, and regulatory issues. He has three decades of industry experience spanning all life science and is an active contributor to FDA’s Case for Quality Initiative. Dan is also a member of the FDA’s advisory council on modeling, simulation, and in-silico clinical trials and co-chaired the Product Quality Outcomes Analytics initiative with agency officials.

Kir Henrici

CEO, The Henrici Group

Kir is a life science consultant working domestically and internationally for over 12 years in support of quality and compliance for pharma and biotech. Her deep belief in adopting digital technology and data analytics as the foundation for business excellence and life science innovation has made her a key member of PDA and ISPE – she currently serves on the PDA Regulatory Affairs/Quality Advisory Board

Oliver Hesse

VP & Head of Biotech Data Science & Digitalization, Bayer Pharmaceuticals

Oliver Hesse is the current VP & Head of Biotech Data Science & Digitalization for Bayer, based in Berkeley, California. He has a degree in Biotechnology from TU Berlin and started his career in a Biotech start-up in Germany before joining Bayer in 2008 to work on automation, digitalization, and the application of data science in the biopharmaceutical industry.

John Maguire

Director of Manufacturing Sciences, Sanofi mRNA Center of Excellence

With over 18 years of process engineering experience, John is an expert in the application of process engineering and operational technology in support of the production of life science therapeutics. His work includes plant capability analysis, functional specification development, and the start-up of drug substance manufacturing facilities in Ireland and the United States.

Chris Kopinski

Business Development Executive, Life Sciences and Healthcare at AWS

As a Business Development Executive at Amazon Web Services, Chris leads teams focused on tackling customer problems through digital transformation. This experience includes leading business process intelligence and data science programs within the global technology organizations and improving outcomes through data-driven development practices.

Tim Adkins

Digital Life Science Operations, ZÆTHER

Tim Adkins is a Director of Digital Life Sciences Operations at ZÆTHER, serving the life science industry by assisting companies reach their desired business outcomes through digital IT/OT solutions. He has 30 years of industry experience as an IT/OT leader in global operational improvements and support, manufacturing system design, and implementation programs.

Blake Hotz

Manufacturing Sciences Data Manager, Sanofi

At Sanofi’s mRNA Center of Excellence, Blake Hotz focuses on developing data ingestion and cleaning workflows using digital tools. He has over 5 years of experience in biotech and holds degrees in Chemical Engineering (B.S.) and Biomedical Engineering (M.S.) from Tufts University.

Anthony DeBiase

Offering Manager, Rockwell Automation

Anthony has over 14 years of experience in the life science industry focusing on process development, operational technology (OT) implementation, technology transfer, CMC and cGMP manufacturing in biologics, cell therapies, and regenerative medicine.

Andy Zheng

Data Solution Architect, ZÆTHER

Andy Zheng is a Data Solution Architect at ZÆTHER who strives to grow and develop cutting-edge solutions in industrial automation and life science. His years of experience within the software automation field focused on bringing innovative solutions to customers which improve process efficiency.

Sue Plant

Phorum Director, Regulatory CMC, Biophorum

Sue Plant is the Phorum Director of Regulatory CMC at BioPhorum, a leading network of biopharmaceutical organizations that aims to connect, collaborate, and accelerate innovation. With over 20 years of experience in life sciences, regulatory, and technology, she focuses on improving access to medicines through innovation in the regulatory ecosystem.

Yash Sabharwal​

President & CEO, QbDVision

Yash Sabharwal is an accomplished inventor, entrepreneur, and executive specializing in the funding and growth of early-stage technology companies focused on life science applications. He has started 3 companies and successfully exited his last two, bringing a wealth of strategic and tactical experience to the team.

Joschka Buyel

Senior MSAT Scientist at Viralgen, Process and Knowledge Management Scientist at Bayer AG

Joschka is responsible for the rollout and integration of QbDVision at Bayer Pharmaceuticals. He previously worked on various late-stage projects as a Quality-by-Design Expert for Product & Process Characterization, Process Validation, and Transfers. Joschka has a Ph.D. in Drug Sciences from Bonn University and a M.S. and B.S. in Molecular and Applied Biotechnology from the RWTH University.

Luke Guerrero

COO, QbDVision

A veteran technologist and company leader with a global CV, Luke currently oversees the core business operations across QbDVision and its teams. Before joining QbDVision, he developed, grew, and led key practices for international agency Brand Networks, and spent six years deploying technology and business strategies for PricewaterhouseCoopers’ CIO Advisory consulting unit.

Gloria Gadea Lopez

Head of Global Consultancy, Business Platforms | Ph.D., Biosystems Engineering

Gloria Gadea-Lopez is the Head of Global Consultancy at Business Platforms. Using her prior extensive experience in the biopharmaceutical industry, she supports companies in developing strategies and delivering digital systems for successful operations. She holds degrees in Chemical Engineering, Food Science (M.S.), and Biosystems Engineering (Ph.D.)

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